The California Stem Cell Agency: 'Envy of the World, ' Hopes Too High?

The prestigious journal Nature yesterday published a piece about California's $3 billion stem cell agency that spoke of voids, envy and "double-edged swords."

The opinion piece was written by Jeanne Loring, a San Diego area

Jeanne Loring

researcher who has followed the agency for years and has been one of its beneficiaries($17 million in awards).

Reflecting on the agency's importance, she wrote,

"For the past dozen or so years, stem-cell researchers in California have been the envy of the world."

Creation of the agency, known formally as the California Institute for Regenerative Medicine (CIRM), "essentially guaranteed that the state would become the center of innovation in the field," Loring declared. Its demise would leave a major void, she said.

Loring continued,

"Although its intentions were laudable, CIRM raised the hopes of the public too high. It needed catchy advertising to gain voters’ support. One of its campaign slogans was 'Save lives with stem cells.' Effective advertisements often focus on a promise and downplay shortcomings, such as the time and resources required to advance a stem-cell therapy through clinical trials to market approval. No CIRM-supported therapy has been approved by the US Food and Drug Administration (FDA), resulting in dashed expectations.... 

"Still, fulfilment of the campaign promise is under way. CIRM has granted funding for 56 stem-cell-based clinical trials."

At the same time, dubious and unregulated clinics that peddle stem cell "snake oil" have proliferated across the country, leading the FDA to attempt a belated takedown of some of the enterprises.

The growth of those clinics is part of "the double-edged sword that is CIRM’s legacy,"  Loring said.

"The agency has enabled fundamental science and helped to establish know-how for rigorous assessment of stem-cell therapies. Earlier this year, my colleagues and I started a biotechnology company, Aspen Neuroscience in La Jolla, California, and are raising funds for a clinical trial of a neuron-replacement therapy for Parkinson’s disease. Without the work that CIRM has done to educate investors and researchers, this would have been very difficult. 

"But the agency’s work has inadvertently helped to boost unregulated, for-profit ‘clinics’ claiming, without sound evidence, that cells derived from fat, bone marrow, placenta and other tissues can cure any disease."

Loring said,

"CIRM has regularly denounced these clinics, which existed before the institute’s creation and will persist as long as they can make money. Still, it is easy to understand how public enthusiasm would spill over to those offering quackery."

Loring noted that the agency, which expects to run out of cash for new awards this year, is hoping that voters will give provide $5 billion more via a ballot initiative in November 2020. 

Loring urged rhetorical caution in the ballot campaign.

"We must strike a balance between future potential and current reality when we talk to the public. Researchers should emphasize that even when therapies show promise in mice, they often fail to work in humans. The only way to find out — and to check for safety — is rigorous scientific testing in clinical trials."

"We need to temper public hope," Loring wrote, while regulators, including the FDA and the California State Medical Board, bring the bad actors under control. 

Stem Cell Hype: The Latest Warning from Researchers

The Scientist journal last week carried a cautionary note concerning iPS cell therapies, particularly a recent, "exciting" announcement concerning their use for treatment of spinal paralysis.

"Ethical Challenges in Using iPS Cells to Treat Paralysis," was the headline on the opinion piece. It carried a subheading that said,

"Uncertainties about the cells’ risk profiles and the potential for hyping unproven therapies mean scientists and the media must tread carefully."

The article dealt primarily with what it termed "exciting" news about an experiment in Japan. But the article has broader implications for the entire field including in California, where the state stem cell agency is currently helping to fund 46 research projects involving iPS, induced pluripotent stem cells. 

The piece was written by John D. Loike, a professor of biology at Touro College and University Systems in Brooklyn and who has a regular column on bioethics in The Scientist, and Martin Grumet, a professor of cell biology and neuroscience at Rutgers.

Writing about the Japanese research, they said, 

"Caution is warranted here, for at least three reasons: the uncertainty of the stem cell type to be used in their clinical trial, the safety of transplanting stem cells into humans, and the responsibility of scientists and the press to communicate clearly the benefits and risks of the stem cell treatments, especially to desperate patients who would seek such unproven treatments."

They continued.

"The excitement of the press release may be misinterpreted by patients, who may think that now is the time to treat human spinal cord injury with stem cell transplants. With difficulties getting admitted to legitimate sub-clinical trials, could this hype for hope lead poorly informed patients to seek out other “stem cells” to treat their spinal cord injuries or other conditions? We must avoid anything that may promote “medical tourism” to unapproved interventions.

"The fact that there are more than 700 'stem cell clinics' advertised in the United States alone highlights the desperation of so many patients with terminal illnesses seeking unapproved or unproven therapies. There are no studies documenting the therapeutic successes of these clinics and some of their patients have developed serious side effects. Scientists and the press must ensure an ethical and realistic presentation and communication of new and potentially exciting discoveries and caution readers about the realities of initial clinical trials.

The Odd Stem Cell Position of the Golden State: Hype, Hope and Dubious Clinics

The California stem cell agency and the Golden State's robust scientific stem cell community received some notice this week in the the Los Angeles Times, the state's largest circulation newspaper. 

It came in the form of an op-ed article that decried the booming business enjoyed by unregulated stem cell clinics, a field where California leads the nation. The Times says it has 1.4 million readers daily and 2.4 million on Sunday.

Usha Lee McFarling, a Pulitzer Prize-winning journalist and currently an artist in residence at the University of Washington, wrote the article discussing the issues surrounding the dubious clinics and their considerable risks, which do not seem to discourage those seeking help. She said,

"So why do patients keep streaming in for treatments that cost thousands of dollars? Part of the reason, I suspect, is that stem cell research — the serious, scientific kind — has gotten so much hype in recent years. We’ve all heard about how some stem cells have the power to become any type of cell in the body and might one day offer cures for all manner of crippling and degenerative diseases. If you can jump the line, and get those treatments now, why not do it? 

"Here’s why: Because the days of miraculous cures, if they come, are far in the future. Today, there is only one federally approved stem cell product: the limited use of blood-forming stem cells to treat certain blood disorders. Scientists are just beginning to learn how to harness the power of stem cells, and the harsh reality is that clinical trials that could turn that knowledge into effective therapies will take years, if not decades."

McFarling continued, 

"California is in an odd position. It is the state with the most stem cell clinics in the country offering these unproven 'cures.' It also happens to be a world center of serious scientific stem cell research, thanks to a $3-billion ballot initiative, Proposition 71, passed by voters in 2004 to fund research."

She noted the fledgling efforts at the state and national level to deal with the dubious clinics. McFarling wrote, 

"Here’s an idea in the meantime. The many scientists who have benefited from taxpayer support of stem cell research in the state should start speaking out. After all, the hype from proponents of Prop. 71 (which created the state stem cell agency) is part of what created such high expectations for quick cures – and eagerness on the part of patients to get them. Scientists should now take every opportunity both to explain to the public the long-term goals of their research and the absurdity of the so-called cures now flooding the market."

Our take: Her advice to California researchers is sound. However, it should be noted that a number of researchers, notably Paul Knoepfler at UC Davis, have been sounding warnings for years. The mainstream media, meanwhile, largely ignored the problem. It took two scientists to do the legwork, which could have been done by journalists as well, that has been the key building block behind the current regulatory efforts, which are still in their infancy.

The Reality of Stem Cell Research vs. Results: A Scientist/Blogger Speaks Out on California's Efforts

A researcher writing on the web site of Science Translational Medicine weighed in last week on California's $3 billion stem cell agency, raising questions about its progress, hype and the fate of the nearly 14-year-old effort. 

In an item Sept. 28 on the blog "In The Pipeline," Derek Lowe said, 

"It’s not like the CIRM money has all been wasted, of course. There’s been a lot of basic research done, and there certainly has been a lot that needed to be done. The amount of brush to be cleared in human developmental cell biology is just monumental. A quick thought the way that all of your body, all the bodies of every human being, comes each from their own single cell will make that clear. If you want stem cell therapies to regenerate organs – as who doesn’t – then you’re asking for a thorough understanding of that process. You may well be asking to do even more than it can tell us how to do."

CIRM is the California Institute for Regenerative Medicine, as the agency is formally known. Lowe's brief bio on the the site says he has worked for "several major pharmaceutical companies since 1989 on drug discovery projects."

The occasion for his remarks was the recent lengthy look at the agency by the San Francisco Chronicle at CIRM and its performance. Lowe wrote, 

"What’s happened? What you’d have expected, if you knew the field at all (or were familiar with basic research in general). None of the bigger promises made during the campaign to fund the CIRM have come true. No approved therapies have come out of the work yet – and that’s one of the class of promises that were most egregious, in California and elsewhere. Just imagine the time it takes from discovery to approval for something like this, and then factor in that the needed discovery hadn’t even been made yet. But if you don’t know anything much about stem cells, or regulatory approvals, or medicine in general, the idea of get-out-of-that-wheelchair cures being just around the corner becomes more plausible."

Lowe also noted that voters may be asked in 2020 to provide more billions for the agency. He said, 

"If you measure it (the agency's work) against what was known and what had been accomplished then versus what’s been done since, you can make a case, for sure. If you measure it against the promises made at the time, though, things look bad. And that informs how you’re going to campaign for renewal: do you point at what’s been done and make the argument that it’s been a success, or do you promise them miracle cures again, because now they just have to be around the corner after all this work, eh?"

Lowe's article received comments from nine readers, who appear also to be researchers. One, who was identified as Miguel Sanchez, wrote, 

"Just at my small CA research institute, the amount of poor science that has been funded by CIRM is staggering. I would say that roughly half the CIRM money we have received has gone to research programs that are prima facie bad science but the PIs are well connected so hey shut up. I don’t think any outright fraud has been published, but the taxpayers of CA are for damn sure not getting their moneys worth on these investments here."

Sanchez did not further identify his employer. The agency's list of grantees did not contain Sanchez's name. 

San Francisco Chronicle: California's $3 Billion Stem Cell Program Does Not Measure Up to Voter Expectations

The San Francisco Chronicle, in a long and penetrating look at California's $3 billion stem cell agency, today said the research program has fallen "far short" of the promises made by its backers during the ballot campaign that created the effort.

Written by Erin Allday and Joaquin Palomino, the article said the agency, created by Proposition 71 in 2004, "can take credit for some notable progress," including saving the lives of children with rare immune deficiency diseases. Such efforts have been well supported by the agency, formally known as the California Institute for Regenerative Medicine (CIRM).

"But as thrilling as such advances are, they fall far short of what Prop. 71’s promoters promised." Allday and Palomino wrote.

"Not a single federally approved therapy has resulted from CIRM-funded science. The predicted financial windfall has not materialized. The bulk of CIRM grants have gone to basic research, training programs and building new laboratories, not to clinical trials testing the kinds of potential cures and therapies the billions of dollars were supposed to deliver."

Allday and Palomino worked on the CIRM overview for months, along with three other major pieces on stem cell therapies, both unregulated and those backed by the stem cell agency.  They reviewed the nearly 1,000 grants awarded by the agency and tracked the results, interviewing researchers and patient advocates and quantified the results.

The Chronicle series appeared as the agency nears its financial demise. It expects to run out of cash for new awards next year. The agency hopes that voters will approve a yet-to-be-written, $5 billion ballot measure in November 2020.

The Chronicle noted, however, that much of the research financed by the agency is not likely to resonate with voters.

Nonetheless, the article today contained ample information from the agency about its efforts, including its 49 clinical trials and some high profile results from those trials.  The piece posed the question of whether the nearly 14-year-old program has paid off. And it said,

"It’s not a question that can be answered simply. Science often can’t be measured in quantifiable outcomes. Failures aren’t just common, they’re necessary — it’s impossible to expect every dollar invested in research to lead down a traceable path toward success.... 

"It has helped make California a global leader in the field that’s come to be known as regenerative medicine. Anywhere significant stem cell research is taking place in the state, it almost surely has received support from CIRM."

The Chronicle quoted a member of the CIRM board who has been with it since its first days.

"'What was promised was not deliverable,' said longtime CIRM board member Jeff Sheehy, a former San Francisco supervisor. 'However, I would distinguish the promises from the impact and value. We have developed a regenerative medicine juggernaut.'"

The Chronicle also spoke with Bob Klein, a Palo Alto real estate investment banker who led the 2014 campaign.

"Klein...is unapologetic about the campaign he led. Indeed, as he lines up advocates and testimonials for the coming campaign, his message is familiar: Fund this research and we will save lives. Slow it down and the consequences will be grave.

"'Do you want your son to die? Are you going to wait?' Klein asked recently. 'Is that the price you are prepared to pay?'"

Today's Chronicle piece, roughly 5,000 words long, raises a host of important issues and deals with them in a nuanced and thoughtful manner. It is must reading for all those interested in California's stem cell research effort. 

(Editor's note: An earlier version of this item inadvertently omitted Palomino's name. Allday noted in an email to the California Stem Cell Report: "He played a HUGE role in putting together the CIRM story – he was basically solely responsible for collecting and analyzing the data from CIRM.")

Exploring California's $210 Million Search for a Sickle Cell Cure, Plus an Online Look at Stem Cell Over Excitement

CIRM mounted another Facebook Live event last week, which has
chalked up nearly 2,000 views.

Hype, hope and sickle cell anemia -- all were part of Internet videos last week involving the $3 billion California stem cell agency.

The San Francisco Chronicle mounted one and the stem cell agency the other. The Chronicle's production was hosted by Erin Allday, the reporter at the newspaper who wrote its ongoing series, The Miracle Cell, dealing with stem cell treatments. (The next installment is scheduled for publication on Thursday and is expected to evaluate the agency itself.)

Allday asked Maria Millan, CEO of the agency, and Paul Knoepfler, a researcher at UC Davis, about the juggling act needed when the benefits and progress of stem cell research are discussed. Both Millan and Knoepfler said it is easy to get overexcited by the progress of stem cell research.

The agency, formally known as the California Institute for Regenerative Medicine (CIRM), produced the second video, a Facebook Live event that so far has drawn more than 1,900 views. Similar figures were not available for the Chronicle video.

Featured on the CIRM video are Donald Kohn of UCLA and Mark Walters of the research institute at Children's Hospital Oakland, along with patient advocate Adrienne Shapiro. The agency has invested $210 million into efforts to find a cure for the disease that afflicts 80,000 people nationally.

Stem Cells, Long Odds and the 'Invisible Hand of Hype'

The headline on the California story pretty much told it all: "Stem Cells: Where Science, Hope and Hype Meet."

It could have added that it is also a meeting place for Big Pharma, Big Academia and Big Politics.

All of those yeasty ingredients are embodied in the $3 billion California stem cell agency, which is plugging away at developing a therapy promised to voters 11 years ago during a $36 million ballot campaign..

The headline appeared on the KQED Web site, a public television and radio outlet in San Francisco. The city, coincidentally, is where the world's largest aggregation of stem cell researchers, the International Society for Stem Cell Research (ISSCR), is meeting today. The conference is also just across the San Francisco Bay from Oakland, where the stem cell agency is headquartered.

Danielle Venton wrote the article for KQED. She covered a bit of the history of the California Institute for Regenerative Medicine or CIRM, as the agency is formally known. She noted that the agency is now participating in 16 clinical trials, although it has yet to chalk up production of a commercial therapy.

Venton wrote,

"(T)he frustration many voters feel about CIRM may have more to do with the problematic way researchers, institutional communicators and the media talk about scientific progress in general, and stem cells in particular, than it does with the agency’s performance.

Timothy Caulfield

"'There has always been this high-stakes, extreme rhetoric around stem cells,' says Timothy Caulfield, who teaches science and health policy at the University of Alberta. Caulfield says because stem cell research was so embattled, many spoke of its promise in hyperbolic terms.

"'People had to make bold statements about the future of stem cells in order to counteract those that wanted to have strict laws to stop it. So you have to say, ‘This is going to save lives. This is going to cure a variety of diseases.’ Right from the beginning, the late ’90s, you have that language appearing in the popular press.”  

Venton reported that the international scientists' group, the ISSCR, is "trying to tone things down" with new guidelines about how to talk about stem cell research and its impact. She said the effort "may be facing long odds." She quoted Caulfield as saying,

“It’s really the invisible hand of hype. In most cases these pressures are largely unconscious — whether you’re talking about the media, the researchers, the institutions or the funding agencies.”

A "Chicken in Every Pot" -- Stem Cells and the Latest Warnings About Hype

Let's face it, folks, without some hype, California's $3 billion stem cell research effort would not exist.

That's because it is a creature of a popular vote in 2004, and the Golden State's voters needed to be persuaded to pony up their billions for something that they were told would pay off and pay off relatively quickly.

Old news, right? But not entirely. Last week the world's foremost stem cell research organization, the International Society for Stem Cell Research (ISSCR), issued stern warnings about "communications" involving stem cell research. "Circumspect and restrained" were the watchwords from the more than 4,000-member group. Seek "timely corrections" of misleading information in the media, the world's stem cell researchers were told, among other things.

All of which is interesting coming from the ISSCR, which loaned its considerable clout in 2004 to the $36 million effort to convince Californians to create the state's stem cell agency with billions borrowed by the state. The effort was also endorsed by a host of individual, top researchers. The campaign is widely regarded as over-promising results on an unrealistic timetable. (See here and here.)

That said, electoral campaigns are not science. Think about promises of a "chicken in every pot," and you will have a good idea of what needs to be said to win an election. And there's the rub.

To generate cash from citizens, it is necessary to create some excitement. Otherwise, it is ho-hum time. One Canadian writer, Kelly Crowe, put it this way in a piece on the public relations guidelines from the ISSCR,

"Would you read a story if this was the headline: 'New study raises questions about an experimental treatment that might not work and won't be ready for a long time.'"

Beyond public perceptions, there is the small matter of stimulating business interest in turning stem cell research into cures, the mission of the California stem cell agency. Businesses are often portrayed as daring innovators bringing fresh, exciting stuff to all of our homes. The reality is that businesses are more often timid, unwilling to take risks that might affect their financial well-being.

So they too must be shown the stem cell light by the agency and its backers so that industry will cough up the considerable cash necessary to bring a stem cell therapy to market and fulfill the promises made to voters 12 years ago.

Just how far should stem cell advocates go in promoting their cause? The ISSCR has its new guidelines. Others may disagree. One person's hype is another person's honest belief. It is unlikely that the ISSCR guidelines will settle the questions.

Little doubt exists that stem cell hype is rampant, some of it from the scientific community and some from enterprises offering untested procedures and treatments. The hype has a natural audience. The public tends to want to believe in scientific and medical miracles, and stem cells smack of miracles.

Randy Mills, the president of the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, regularly brings the facts of "risk" to his dealings at the agency. It is one of his finer innovations.

Last year, his plan for the agency's next five years contained three pages of "risks," including inadequate health benefits, foot-dragging by the federal regulators and safety issues.

Mills exudes excitement for stem cell research and its potential, but at the same time he has a keen eye for the obstacles. It could be called realism. Unless you see the obstacles, you cannot hurdle them. Nor can the public be expected to be patient if it is oversold and under-delivered. 

(A final note: Kelly Crowe's piece is a dandy and involves much more than stem cell research. The headline: "It's not just stem cell research that's overhyped— medical science spin is a widespread problem.")

Inside STAP: New Yorker's Long Look at the Flap and its Implications

Over the weekend, the New Yorker published online a bang-up and thorough account of the STAP stem cell scandal of 2014. which stretched across the Pacific from Japan to Boston.

The subhead on the story said,

“Rivalries, intrigue, and fraud in the world of stem-cell research”

The piece was authored by Dana Goodyear, a writer for the New Yorker who also teaches writing at the University of Southern California.

UC Davis stem cell researcher Paul Knoepfler, who carried on his blog early and lengthy pieces on the STAP flap, today said of the article:

“It’s a long, fascinating look inside of STAP, the tangled and ultimately tragic scientific implosion that created and then brought down two Nature papers and some careers.”

Goodyear’s article brought out much fresh material, including a more detailed look at the history of the STAP research than has been previously published. The piece also contained probably enough scientific detail to satisfy the experts in the field.

But Goodyear also included thoughts on the stem field in general, issues related to scientific journals, hyper-competitiveness among researchers, replication of research and more. Here are a couple of excerpts from the article, which we highly recommend:

“The promises of stem-cell research lie at the core of human desires—to understand our origins and to cheat death—and there is a great deal of money and prestige at stake. It is a ruthlessly competitive field, susceptible to fantasy and correspondingly sensitive to bunglers. Human embryonic stem cells were first cultured in 1998; nearly twenty years later, basic assumptions about cell behavior are still routinely overturned. Andrew McMahon, a top researcher at the Broad Center for Regenerative Medicine and Stem Cell Research, at the University of Southern California, told me, “It’s not unusual to see something and not be able to explain it.” In reporting results, researchers must often craft a narrative to make sense of mysterious phenomena. What to ignore and what to privilege—that discernment can be the difference between brilliance and quackery, and between fame and obscurity.”

On the difficulties in replicating research findings:

“Many people believe this is partly the fault of the scientific journals. Along with the influential role that Nature has in shaping the trajectories of ideas, technologies, and careers, it is essentially a commercial enterprise. The editors like big stories, and for the right ones they take risks. Some observers complain that incentives to publish have a distorting effect, causing scientists to oversell data; a cutthroat culture sometimes leads researchers to publish intentionally incomplete or vague protocols. The perceived conflict between good science and prestige has become so pointed that, two years ago, Randy Schekman, a Nobel Prize-winning biologist, announced in the Guardian that he would no longer publish in Nature, Cell, or Science, which, he wrote, ‘aggressively curate their brands, in ways more conducive to selling subscriptions than to stimulating the most important research.’”

'Born in Hype:' The California Experiment and Stem Cell Research

A California newspaper with a daily readership of 1.5 million this week thrashed the field of stem cell science, declaring that it “is slathered with so much money that immoderate predictions of success are common.”

“Infected with hype” is the way the headline put it on the March 31 piece in the Los Angeles Times. The paper has the largest circulation in the state and is an agenda-setter for much of the state’s mainstream media.

The comments came in an article by Pulitzer Prize-winning columnist and author Michael Hiltzik, who holds the California stem cell agency in low regard.

Kalina Kamenova
 U. of Alberta photo

Timothy Caulfield
U. of Alberta photo

His starting point was a study in Science Translational Medicine by Timothy Caulfield and Kalina Kamenova of the University of Alberta law school.  Their content analysis research focused primarily on newspaper coverage of timelines for stem cell therapies before and after Geron bailed out of the first clinical trial for a human embryonic therapy in the United States. They did not have warm words for scientists as public communicators.

Neither did Hiltzik, but he also faulted the media. He wrote, 

“The authors mostly blame the scientists, who need to be more aware of ‘the importance of conveying realistic ... timelines to the popular press.’ We wouldn't give journalists this much of a pass; writers on scientific topics should understand that the development of drugs and therapies can take years and involve myriad dry holes and dead ends. They should be vigilant against gaudy promises.”

Hiltzik then took on the California Institute for Regenerative Medicine (CIRM), as the stem cell agency is known.  He wrote about the cash that was "slathered" about. He said,

“The best illustration of that comes from California's stem cell program -- CIRM, or the California Institute for Regenerative Medicine -- a $6-billion public investment (including interest) that was born in hype. 

“The promoters of Proposition 71, the 2004 ballot initiative that created CIRM, filled the airwaves with ads implying that the only thing standing between Michael J. Fox being cured of Parkinson's or Christopher Reeve walking again was Prop. 71's money. They commissioned a study asserting that California might reap a windfall in taxes, royalties and healthcare savings up to seven times the size of its $6-billion investment. One wouldn't build a storage shed on foundations this soft, much less a $6-billion mansion.”

 He wrote about how CIRM played a dubious role in funding the Geron clinical trial only a couple of months before the company pulled the plug for financial reasons, something that the California Stem Cell Report has dealt with as well.  The $26 million loan to Geron involved a major departure from the agency’s normal procedures.  Abandonment of the trial also raised ethical questions that should be of continuing concern to the agency and its ethical advisors who are meeting today and tomorrow in Los Angeles.  

Caulfield’s views on stem cell hype are well-known in the small stem cell research community. But rarely does his sort of perspective, which is shared by others in the field, reach a mass audience such as the 1.5 million readers of the Los Angeles Times.

All of which poses a challenge for the California stem cell agency whose finite amount of cash is now expected to run out in 2020. As Hiltzik noted, the overblown expectations led voters to believe that miraculous cures were just around the corner.

Today, more than a decade after creation of the agency, the promised cures have not materialized and none are likely for some years. The agency has undoubtedly made a major contribution to stem cell science. But the unfulfilled promises of the campaign hype gave its foes the kind of tools they need to battle any efforts to provide more state funding for the agency.  How CIRM deals with that scientific and PR challenge will be one of the major tests for it over the next several years.

California Stem Cell Research: Juggling Safety and Speed

Robert Klein, the first chairman of the California stem cell agency, is a relentless salesman for the potential of stem cell research.

Certainly such was the case on Nov. 20 when he and a host of others celebrated the 10th anniversary of the Golden State’s $3 billion research effort. Klein said the dream of patients has already become a reality.  But Klein, as he has done in the past, also warned that there would be setbacks.

He might be called prescient. One day later, news emerged from Great Britain about the deaths of four children involved in a stem cell transplant.

It was a reminder that there are considerable risks involved in the field, which is often viewed uncritically by patients and the public. In the case of the British children, Owen Bowcott of The Guardian reported on Nov.25 that the exact cause of the problem with the treatment is still not known.  The cells involved passed all the normal protocols, however.

The California stem cell agency is now involved in 10 clinical trials of stem cell treatments. These are very early stage trials primarily involving safety. The agency will be pushing aggressively and rapidly in the next few years for more trials. “We need a home run,” said Sherry Lansing, a member of the board of directors of the agency, late last year.

The agency is expected to run out of money for new grants in 2020, a date that has been revised from 2017.  Future funding will depend in large part on marketable successes that resonate with future potential sources of funding, be they private or the general public via another bond issue.

Balancing speed with care and safety can be a difficult task. But a catastrophic event can squash the agency’s efforts just as thoroughly as the lack of home runs.

BS and Ebola, Hype and Stem Cells

Hyperbole surrounding both stem cells and Ebola research has surfaced recently with cautionary notes concerning the damage it can do to the reputation of researchers and science.

Just last week UC Davis stem cell scientist Paul Knoepfler took up the matter in a piece headlined “The Cheating Death Excitation.” Over on the Pacific Standard Web site, Michael White of the Washington University School of Medicine wrote an article titled “Why Scientists Make Promises They Can’t Keep.”

White’s entry point was a flap last month about whether more federal funding would have meant faster progress on an Ebola vaccine. The hooha started with a statement by Francis Collins, head of the National Institutes of Health, and included a retort by Michael Eisen of UC Berkeley that Collins’ comments were “complete BS.”

Subheads in White’s Oct. 31 piece summarized his view nicely,

“A research proposal that is totally upfront about the uncertainty of the scientific process and its potential benefits might never pass governmental muster.”

“We, scientists and society, need to be more honest about the uncertainty inherent in the scientific process and in any projection of society’s future needs.”

Out west in California, Knoepfler remarked Nov. 6 on his blog,

“Can stem cells help many people in the immediate future to escape death? Recent headlines on new stem cell-related clinical developments would make you think so and they go a step further to indicate that such miracles are just around the corner.”

He continued,

“In the last few weeks there’ve been an unusually large number of papers and newspaper headlines about stem cell clinical developments, and as much as I hate to say it as an advocate for the stem cell field, many of these cases have been hyped.

“The reporters, their headlines and in some cases even some of those involved in the research seemingly would like you to think that cures for all kinds of bad things are about to happen tomorrow.”

Knoepfler said stem cell technology will be important and it will lead to “humanity changing events…but we aren’t there yet.”

“It’ll probably take another decade or two to really get closer to being a reality. Raising expectations sky high right now with over-the-top claims and headlines is not helpful to progress.”

Our comment: In the case of the $3 billion California stem cell agency, it has been burdened by the hype of the 2004 ballot campaign that created it. Voters were led to believe that miracles were in the offing and only 10 years or less away. That perception has not served the agency or the people well. Nor does it enhance the credibility of stem cell researchers, who were largely silent in 2004 about the grindingly slow process of science and government regulation of new treatments. Yes, ballot campaigns do need to generate excitement and hope. They also have a propensity to degenerate into falsehoods, critical omissions and exaggeration. That is one good reason that expensive ballot campaigns ($35 million in the case of the stem cell agency) are not necessarily the best way to fund scientific research.

As Knoepfler said,

“The key is balance….get excited and talk about the cool stem cell work (but) temper your statements a bit and keep plugging away at the research.”

Expectations, Ballyhoo and Stem Cell Research

Two seemingly unrelated biotech stories popped up this morning on the news.  One involved an international stem cell research brouhaha. The other involved what could amount to a nearly $2 billion biotech deal for a California firm.  

What brings them together is the diaphanous nature of some of the work in these much ballyhooed fields. But first, let’s look at the latest reports about the STAP stem cell flap concerning research in Japan and Massachusetts that seemed to promise a fast and easy way to make pluripotent stem cells.

After five months and major questions, the journal Nature has decided to retract the STAP paper despite the fact that the journal had it vetted by some of the best scientists in the world. Even with the review, Nature said “extensive” errors have surfaced along with “inexplicable discrepancies.”

It is fair to say that 20 years ago, that paper would still be widely accepted and remain firmly entrenched in Nature’s archive as reliable. What has changed is the Internet and impact of social media on evaluation of research. That has given researchers the unfettered ability to discuss and publish their findings dealing with replication of results and other issues.  At the same time, the speed in which this cyber review takes place is remarkable.  The change from 20 years ago is the equivalent of the move from hand-cranked printing presses to the high-speed presses of today that can spit out thousands of pages an hour.

(We should note that California stem cell researcher Paul Knoepfler of UC Davis played an important role in probing the scientific reliability of the STAP research with responsible reporting and commentary on his blog, ipscell.com.)

Now, about that nearly $2 billion deal, Wall Street Journal columnist Helen Thomas this morning wrote about the acquisition of Seragon Pharmaceutical by Roche, describing it as “disconcerting.” She said it could be a case of shelling   “out vast sums for assets that could quite possibly amount to nothing.”  San Diego-based Seragon “was formed only last year and has one breast cancer drug in early stage trials,” Thomas wrote.

She continued,

“The global pharma sector's forward earnings multiple has expanded to almost 16 times, up from less than 11 times two years' ago, in part because investors believe the (biotech) industry's R&D machine is again producing the goods.”

Thomas noted, however, that only one in 10 potential therapies entering clinical trials reaches the marketplace. “The risks are substantial,” she said. Those same risks apply as well to the 10 clinical trials that the California’s $3 billion stem cell agency has been involved in.

Earlier this year, noted bioethicist Art Caplan wrote about what he called the “off-the-rails syndrome” in stem cell research. The STAP article was his starting point.  Stem cell research is a field that has had more than its share of hype. Well-respected scientists routinely refer to its revolutionary potential. Little public attention is paid to the obstacles and the lengthy and often unsuccessful process of developing a truly usable product.  Expectations of desperate patients are raised. Many of them wind up paying for expensive, untested and perhaps unsafe treatments.

The Seragon-Roche deal is also a reflection of the hype that can arise in biotech/stem cell research. It can be so powerful that the supposedly “rational” economic markets are swept up in the exuberance of a nifty research story.  Ultimately the deal may pan out for Roche, although Roche can afford to take a big loss. But stories are stories.

What does all this mean for the California stem cell agency? Good reasons exist to manage expectations so that the public and potential sources of funding are surprised by successes rather than being surprised by the agency’s failures.  No one wants to see a story like the Solyndra scandal emerge from the California stem cell agency.